Although hybridoma technology opens the prospect of the development for therapeutic uses of unlimited quantities of homogeneous and highly specific antibodies directed against tumor specific antigens, an alternative immunotherapeutic use for monoclonal antibodies will be explored in the animal model to be developed. This model involves the production of antiidiotypic monoclonal antibodies against T lymphocyte receptors for tumor-specific or tumor-associated antigens. These antibodies may be used to induce T lymphocyte-mediated immunity to the tumor. (Balb/c x C57BL/6)F1 mice will be immunized against the H-2d lymphoma RL-male 1 and tumor-responsive T lymphocytes will be cloned and propagated in the presence of feeder cells and growth factors. Clones will be the source of receptor-bearing lymphocytes for the production in (Balb/c x C57BL/6)F1 mice of antibody-producing cells to be fused and cloned in the generation of hybridomas. Monoclonals generated will be tested for antiidiotypic specificity; those with specificity for combining site will be tested for capacity to induce tumor immunity in virgin animals. Phase one of the project will involve production of the T cell clones, the monoclonal antibodies, and the demonstration of induction of anti-tumor immunity. Phase two will involve the testing of a conceptually crucial hypothesis. The T lymphocytes responsive to the RL-male-1 tumor are H-2 restricted; it is hypothesized that the extent to which immunity induced by antiidiotype will be H-2 restricted will vary with the antiidiotype employed. If the immunity induced is always H-2 restricted then the population will be limited. Phase 3 of the project will involve study of various parameters of the model such as the relevance of the functional properties of the initial T cell clone used as immunogen, the effectiveness of monoclonals of various isotype, and the influence of dose and schedule of monoclonal administration. These studies will have important significance for the development of comparable reagents for human cancers, with the greatest immunotherapeutic potential most likely existing in the adjuvant setting.